Excellent outcome of acute lymphoblastic leukaemia with <i>TCF3‐PBX1</i> rearrangement in Hong Kong

Lin, Anna; Cheng, Frankie Wai Tsoi; Chiang, Aks; Luk, Chung-Wing; Li, Rever C. H.; Ling, Alvin Siu-Cheung; Cheuk, Dkl; Chang, Kai-on; Ku, Dennis; Lee, Vincent; Ha, Shau Yin; Li, Chi Kong

doi:10.1002/pbc.27346

Cited by 16 publications

(19 citation statements)

References 15 publications

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“…Complete remission (CR), BM relapse or extramedullary relapse were defined as standard diagnostic criteria [15,16,17], while EFS was defined as the time from diagnosis to the date of last contact for event-free survivors or to the first adverse event (relapse or refractory disease, death from any cause, secondary cancer or loss to follow-up). Following December 2020, data about the clinical characteristics, laboratory findings, treatment-related mortality (TRM), and EFS of these patients were collected and retrospectively analyzed; NGS detection data for relapsed patients were also collected and analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…The patients received chemotherapy according to the Chinese Children Leukemia Group ALL-2008 protocol (CCLG-ALL-2008, Table-1) [15,16], and all patients received intrathecal injection (iT) for the prophylaxis of CNSL as the protocol required; minimal residual disease (MRD) level monitoring was performed by FCM, and 10 -4 was considered the limitation of MRD monitoring [15,16,17].…”

Section: Treatment Therapeutic Evaluation and Risk Strategymentioning

confidence: 99%

“…At all three TPs, remission status of BM smear was recorded as follows: M1 (leukemic cells <5%), M2 (leukemic cells 5-25%) and M3 (leukemic cells ≥25%)15,16. The MRD level was monitored by FCM on TP2 and TP3 [15,16,17].…”

Section: Treatment Therapeutic Evaluation and Risk Strategymentioning

confidence: 99%

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The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers

Zou

Zhou

Wen³

et al. 2021

Bosn J of Basic Med Sci

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Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.

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Section: Discussionmentioning

confidence: 99%

Section: Treatment Therapeutic Evaluation and Risk Strategymentioning

confidence: 99%

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The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers

Zou

Zhou

Wen³

et al. 2021

Bosn J of Basic Med Sci

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“…Other genes with hypomethylation and corresponding higher expression in t(8;21) vs. other subtypes included: MGMT (methylguanine-DNA methyltransferase), a tumor suppressor gene that has been associated with risk of AML development [ 38 ]; MPL (myeloproliferative leukemia virus oncogene), which has been shown to be essential for survival and self-renewal of human preleukemic t(8;21) cells [ 39 ]. Wildtype MPL has been shown to be overexpressed in t(8;21) AML and promote leukemia development via PI3K/AKT axis activation [ 40 ]; KDM4B , a histone specific demethylase, has been implicated in regulating expression of genes required for maintenance of hematopoiesis [ 41 ]; TCF3 , a fusion partner of PBX1 and 4-HLF in ALL [ 42 , 43 , 44 , 45 ], however its importance in AML is not currently known; and ABR that codes for an Active BCR related is involved in deactivation of RAC1 (ras-related C3 botulinum toxin substrate 1) important for hematopoiesis and leukemia [ 46 ]; we observed hypomethylation and low expression of ABR in t(8;21) ( Figure 2 B). Recently, ABR has been shown to be an enhancer of C/EBPa , a key mediator of myeloid differentiation, associated with azacytidine-induced apoptosis and as a favorable prognostic factor in AML [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Lamba

Cao

Raimondi

et al. 2020

Cancers

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Acute Myeloid Leukemia (AML) is characterized by recurrent genetic and cytogenetic lesions that are utilized for risk stratification and for making treatment decisions. In recent years, methylation dysregulation has been extensively studied and associated with risk groups and prognosis in adult AML, however, such studies in pediatric AML are limited. Moreover, the mutations in epigenetic genes such as DNMT3A, IDH1 or IDH2 are almost absent or rare in pediatric patients as compared to their abundance in adult AML. In the current study, we evaluated methylation patterns that occur with or independent of the well-defined cytogenetic features in pediatric AML patients enrolled on multi-site AML02 clinical trial (NCT00136084). Our results demonstrate that unlike adult AML, cytosine DNA methylation does not result in significant unique clusters in pediatric AML, however, DNA methylation signatures correlated significantly with the most common and recurrent cytogenetic features. Paired evaluation of DNA methylation and expression identified genes and pathways of biological relevance that hold promise for novel therapeutic strategies. Our results further demonstrate that epigenetic signatures occur complimentary to the well-established chromosomal/mutational landscape, implying that dysregulation of oncogenes or tumor suppressors might be leveraging both genetic and epigenetic mechanisms to impact biological pathways critical for leukemogenesis.

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“…RFX1 could be used as a candidate marker molecule for poultry resistance to ALV-J infection. T cytokine 3 (TCF3, also known as E2A) is closely related to human acute lymphoid leukemia [30]. TCF3 protein is highly expressed in Tibetan chicken, suggesting that TCF3 may play the same role as RFX1 in suppressing the immune function of the virus.…”

Section: Discussionmentioning

confidence: 99%

Screening of immune biomarkers in different breeds of chickens infected with J subgroup of avian leukemia virus by proteomic

Wang

et al. 2020

Virulence

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Avian leucosis (AL) is a disease characterized by tumors and is caused by the avian leukosis virus (ALV). Because of the high variability of viruses and complex pathogenic mechanisms, screening and breeding J subgroup of ALV (ALV-J) resistant avian breeds is one of the strategies for prevention and treatment of AL, thus screening of significant immune markers is needed to promote the development of disease-resistant breeds. In this study, data-independent acquisition (DIA) technology was used to detect the DEPs of three breeds of chicken according to different comparison to investigate the potential markers. Results showed special DEPs for spleen development of each breed were detected, such as PCNT, DDB2, and ZNF62. These DEPs were involved in intestinal immune network used in production of IgA signaling pathways and related to immune response which can be used as potential markers for spleen development in different breeds. The DEPs such as RAB44 and TPN involved in viral myocarditis, transcriptional misregulation in cancer, and tuberculosis can be used as potential markers of spleen immune response after ALV-J infection in chickens. Pair-wise analysis was performed for the three breeds after the infection of ALV-J. The proteins such as RFX1, TAF10, and VH1 were differently expressed between three breeds. These DEPs involved in antigen processing and expression, acute myelogenous leukemia, and viral carcinogenesis can be used as potential immune markers after ALV-J infection of different genetic backgrounds. The screening of potential markers at protein level provides a strong theoretical research basis for disease resistance breeding in poultry.

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Excellent outcome of acute lymphoblastic leukaemia with TCF3‐PBX1 rearrangement in Hong Kong

Abstract: This population-based study over the past 20 years demonstrated that patients with TCF3-PBX1 rearrangement had favourable EFS compared with other intermediate risk patients treated with a similar chemotherapy backbone.

Cited by 16 publications

References 15 publications

The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers

The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers

DNA Methylation Clusters and Their Relation to Cytogenetic Features in Pediatric AML

Screening of immune biomarkers in different breeds of chickens infected with J subgroup of avian leukemia virus by proteomic

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